Phosphoinositide signals regulate cell proliferation, differentiation, cytoskeletal rearrangement and intracellular trafficking. Hydrolysis of PtdIns(4,5)P2 and PtdIns(3,4,5)P3, by inositol polyphosphate 5-phosphatases regulates synaptic vesicle recycling (synaptojanin-1), hematopoietic cell function [SHIP1(SH2-containing inositol polyphosphate 5-phosphatase-1)], renal cell function [OCRL (oculocerebrorenal syndrome of Lowe)] and insulin signalling (SHIP2). We present here a detailed review of the characteristics of the ten mammalian 5-phosphatases. Knockout mouse phenotypes and underexpression studies are associated with significant phenotypic changes, indicating non-redundant roles, despite, in many cases, overlapping substrate specificity and tissue expression. The extraordinary complexity in the control of phosphoinositide signalling continues to be revealed.

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Author notes

The Biochemical Society's Annual Symposium, The Cell Biology of Inositol Lipids and Phosphates, was held at the University of Birmingham on 29-31 March 2006.